1) Field of the Invention
The present invention relates to a QCM (Quartz Crystal Microbalance) sensor that that detects an amount of a substance adsorbed on a piezoelectric transducer based on a change in resonance frequency of the piezoelectric transducer, such as an AT-cut quartz resonator, caused by adsorption (attachment) of a small amount of substance on the piezoelectric transducer.
2) Description of the Related Art
The principle of measurement by a QCM sensor device, if the resonance frequency is denoted by f, a difference in the resonance frequency due to the mass (adsorbed) attached is denoted by Δf, and a change in mass is denoted by Δm, the change in the resonance frequency denoted by Sauerbrey's equation (1) disclosed in (pages 918 to 929 of) ‘Development of piezoelectric bio-sensor and latex piezoelectric element immunoassay for clinical examination’ published in pages 917 to 930 of No. 12, Vol. 46 of BUNSEKI KAGAKU (ANALYTICAL CHEMISTRY) (1997) is as follows:Δf=−K·f2·Δm  (1)(where K is a constant depending on the area of an electrode, density, and an elastic constant of a material of the quartz crystal).
It is clear from equation (1) that, if the difference Δf in the resonance frequencies of the AT-cut quartz resonator before and after the adsorption (attachment) of the mass can be measured, it is possible to calculate the mass adsorbed (attached) Δm. Moreover, if a piezoelectric transducer having high resonance frequency is used, it is possible to increase the sensitivity of the mass detection. For example, if a quartz crystal resonator having resonance frequency 9 megahertz (MHz) is used, for a change of 1 nanogram (ng) in mass, there is a change of about 1 Hz in the frequency. In other words, if a quartz crystal resonator is made to oscillate by an oscillating circuit and an output is measured by a frequency counter, it is possible to have simple and highly sensitive measurement of a change in the mass. Moreover, when the quartz crystal resonator is used in a liquid, the resonance frequency changes depending on the viscosity and the density of the liquid so that the viscosity and the density of the liquid can be determined from the resonance frequency.
Gas sensors or odor sensors which can detect even a small amount of toxic material in the atmosphere have been drawing attention. Moreover, in recent years, due to the development in a technology that makes oscillate the piezoelectric transducer in a solution, bio sensors or chemical sensors which sense organic compounds and bio-molecules have been drawing attention (Refer to ‘Examples of Biochemical Acoustic Wave Sensor’ published in pages 307 to 308 of ACOUSTIC WAVE SENSORS by ACADEMIC PRESS (ISBN 0-12-077460-7) and (pages 918 to 929) ‘Development of piezoelectric bio-sensor and latex piezoelectric element immunoassay for clinical examination’ published in pages 917 to 930 of No. 12, Vol. 46 of BUNSEKI KAGAKU (ANALYTICAL CHEMISTRY) (1997)).
Moreover, in recent years, as in the case of analysis of human genome, methods for analyzing a very large number of samples simultaneously and speedily have been established. This has led to an increased demand for high throughput to bio-analytical equipments other than those employing DNA sequencing. Even in QCM sensors, in the field of proteomix (comprehensive analysis of proteins) or drug discovery, there has been increasing need to analyze an interaction between a large number of proteins for all combinations and multi-channeling has been sought.
In conventional QCM sensor devices, devices that measures one sample at a time have been predominant. However, multi-channeling can be realized comparatively easily by arranging a plurality of measurement cells in which the quartz crystal resonators are mounted and arranging simultaneously a measurement circuit that measures the resonance frequency of a plurality of resonators.
In the conventional multi-channel QCM sensors, terminals of a plurality of resonators in which a quartz substrate is arranged in two-dimensions are connected in the form of a matrix. A wiring in the direction of X and a wiring in the direction of Y are switched by a switching circuit like a relay etc. and only a resonator at an intersection of the wiring selected is connected to the oscillating circuit. Thus, the number of wiring was reduced (refer to the technology disclosed in paragraphs 0048 to 0051 and FIG. 3 of Japanese Patent Application Laid-open Publication No. 2000-338022).
In FIG. 3 of the Japanese Patent Application Laid-open Publication No. 2000-338022, reference numeral 51 denotes a multi-channel QCM sensor device provided with a plurality of oscillating domains on a quartz crystal substrate and A to I denote working electrodes and are oscillating domains for each electrode. Rear electrodes are disposed on a rear surface of the oscillating domains. The working electrodes are connected commonly in a vertical direction in the diagram to terminals 521, 522, and 523. The rear electrodes are connected commonly in a horizontal direction to terminals 531, 532, and 533. A vertical wiring is selected by a change-over switch 55 and a horizontal wiring is selected by a change-over switch 56. A working electrode and a rear electrode of an oscillating domain selected are connected to a oscillating circuit or an impedance-measurement circuit 54 and the resonance frequency is measured. A controller 57 specifies the vertical direction and the horizontal direction from a plurality of piezoelectric-transducer (piezoelectric-oscillating) fields and selects one piezoelectric transducer field.
However, in the conventional QCM sensor disclosed in paragraphs 0048 to 0051 and FIG. 3 of Japanese Patent Application Laid-open Publication No. 2000-338022, in nine piezoelectric-transducer fields, 18 wires necessary for leading out to all the working electrodes and the rear electrodes can be reduced to 6 by connecting in the matrix form; however, 6 wires and 2 change-over switches are still required. Furthermore, in Japanese Patent Application Laid-open Publication No. 2000-338022, one piezoelectric-transducer field is selected from a plurality of the piezoelectric-transducer fields and the resonance frequency is measured for the selected piezoelectric-transducer field. The measurement of the resonance frequency has to be repeated as many times as the number of the piezoelectric-transducer fields. Due to this, time required for one measurement point is long. Particularly, when the resonance frequency is measured by the oscillating frequency, it takes a long time for the stopped oscillations to reach stable oscillations. As a result, the time required for measurement becomes long which is a drawback. In addition, an operation of the change-over switch further complicates the measurement.